Influenza A viruses (IAVs) cause seasonal outbreaks and occasional severe pandemics that are a significant burden in morbidity, mortality, and economic loss. The continuous evolution of IAV through mutation and reassortment provide molecular mechanisms to allow IAV to evade host immunity. However, there remain significant gaps in our understanding of the tug of war between host and virus, particularly, the molecular mechanisms influenza virus employs through evolution in response to host defenses and the implications this may have for vaccination strategies. In 2018, by focusing on the biology, evolution and pathogenesis of the virus, we have aimed to determine first the significance and extent of IAV evolution caused by acute primary and memory (vaccination) adaptive immune responses. Specifically, we are utilizing next generation sequencing of the full Influenza virus genome to determine the kinetics and extent of virus evolution. We are determining whether our current vaccination strategies result in enhanced viral evolution and whether the viral evolution rate could be used as an early indicator of vaccine efficacy. Second, we want to elucidate the role of Influenza virus protein evolution in viral pathogenesis and transmission. Through these studies, we aim to further our understanding of IAV evolution and the underlying causative host mechanisms. It is hoped that with a better understanding of the highly adaptive IAV, these studies will uncover novel and improved ways to vaccinate and combat IAV infection.